SLC19A1 p.Phe406=
c.1218T>C · rs150116000 · VCV2045394
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.132%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.5 |
| Overall | ||
| CADD | 0.023 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.132%
Middle Eastern · 8/6,060 alleles
Filtering AF
0.0657%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0479%
Overall
0.0303%
489/1,613,690 alleles · rare
exomes 452/1,461,316 · genomes 37/152,374 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.132% | 758 |
| South Asian | 0.0538% | 1,859 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| European (non-Finnish) | 0.0331% | 3,018 |
| Admixed American | 0.0233% | 4,288 |
| African / African-American | 0.00533% | 18,768 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SLC19A1
- Protein
- p.Phe406=
- Coding
- c.1218T>C
- MANE Select
- NM_194255
- dbSNP
- rs150116000
- Type
- single nucleotide variant
- Location
- chr21:45525892 (GRCh38)
- Gene constraint
- LOEUF 1.585 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.30 · 19 PDB
- Residue 406
- an α-helix
Similar variants
- COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
- COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
- RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
- COL18A1 c.*30G>A Uncertain significance ★★ same type
- COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
- COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
- COL18A1 p.Arg1081Gln Uncertain significance ★★ ⚠ same type
- COL18A1 p.Arg1183His Uncertain significance ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/slc19a1-p-phe406 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown